Wednesday, 30 April 2014

Kir 4.1 may be lost in MS lesions

Schirmer L, Srivastava R, Kalluri SR, Böttinger S, Herwerth M, Carassiti D, Srivastava B, Gempt J, Schlegel J, Kuhlmann T, Korn T, Reynolds R, Hemmer B. Differential loss of KIR4.1 immunoreactivity in multiple sclerosis lesions. Ann Neurol. 2014 Apr 29. doi: 10.1002/ana.24168. [Epub ahead of print]

Objective: Serum antibodies against the glial potassium channel KIR4.1 are found in a subpopulation (5-50% depending on who you believe see below) of multiple sclerosis (MS) patients. Little is known about the expression of KIR4.1 in human normal brain tissue and in MS lesions. 
Methods: We analyzed the expression pattern of KIR4.1 in normal brain tissue and MS lesions of the subcortical white matter by immunohistochemistry. Markers of related glial proteins, myelin and inflammatory cells were analyzed in parallel. 
Results: KIR4.1 is expressed in oligodendrocytes and astrocytes in the adult human brain. In oligodendrocytes, KIR4.1 appears as homotetramer channel, in astrocytes as homo- and heterotetramer channels together with KIR5.1. In acute MS lesions, KIR4.1 immunoreactivity (IR) was differentially lost on periplaque oligodendrocytes and perivascular astrocytes. In part of acute lesions, complement activation, apoptotic KIR4.1+ glial cells and phagocytes containing KIR4.1+ fragments accompanied loss of glial KIR4.1 IR. Periplaque reactive astrocytes showed enhanced IR for both KIR4.1 and KIR5.1. In chronic active MS lesions, apart from a general loss of oligodendrocytes in the demyelinated area we observed a decrease of astroglial KIR4.1 but not GFAP IR. In chronic inactive and remyelinating MS lesions, KIR4.1 IR was restored on astrocytes and found in a subset of presumably new myelinating oligodendrocytes. 
Interpretation:The expression profile of KIR4.1 in glial cells and stage-dependent alterations of KIR4.1 IR in MS lesions are compatible with an immune response against KIR4.1 at least in a subset of MS patients.

If you have antibody responses to Kir4.1 and they can get into the brain yo may have masking of the Kir4.1, which could mask their detection and you could have damage as a result of antibody binding.  The importance depends on whether you think this is a major or minor component of MS.

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